The basic aim of this grant request is to study the relationship between 02 supply and consumption and its variability on a regional basis in heart in normal and ischemic myocardium. We would like to determine three things about ischemic myocardium and how they change with treatments proposed to alter the damage of ischemia. With myocardial ischemia, it is important to determine what happens to regional 02 consumption within the area of ischemia; it is also important to know the relationship of 02 supply to consumption on a regional basis within this area and to understand the regional variability of 02 supply delivery and 02 usage within this ischemic area. To accomplish these ends we have developed a highly accurate microspectrophotometric method for determination of 02 saturation in small arteries and veins in a quick frozen tissue. By combining these measurements with a regional flow determination, regional 02 consumption can be calculated quantitatively for the first time. Measurements will be performed on anesthetized open-chest dogs in which a portion of their heart will be made ischemic by ligation of the left anterior descending coronary artery. We will determine 02 consumption, the 02 supply/02 consumption ratio, and regional heterogeneity in a normal an ischemic region at various time intervals after ligation of the coronary artery. We will then test various agents that have been proposed to both aid and further endanger ischemic myocardium to see how they affect these measurements. It is obvious that agents improve the 02 supply to consumption ratio may be useful. What we would also like to study is how these agents affect microregional heterogeneity of 02 supply and consumption. There are vessel by vessel variations in flow within an ischemic area and also variations in consumption. It is possible that by altering the distribution of flow and consumption, ischemic tissue can be salvaged.